title: Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives.
abstract: The peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders in which peroxisome assembly is impaired, leading to multiple peroxisome enzyme deficiencies, complex developmental sequelae and progressive disabilities. Mammalian peroxisome assembly involves the protein products of 16 PEX genes; defects in 14 of these have been shown to cause PBD. Three broad phenotypic groups are described on a spectrum of severity: Zellweger syndrome is the most severe, neonatal adrenoleukodystrophy is intermediate and infantile Refsum disease is less severe. Another group is Rhizomelic chondrodysplasia punctata spectrum. Recently, atypical phenotypes have been described, indicating that the full spectrum of these disorders remains to be identified. For most patients, there is a correlation between clinical severity and effect of the mutation on PEX protein function. Diagnosis relies on biochemical measurements of peroxisome functions and PEX gene sequencing. There are no targeted therapies, although management protocols have been suggested and research endeavors continue. In this review we will discuss peroxisome biology and PBD, and research contributions to pathophysiology and treatment.
authors.affiliation: Department of Human Genetics, McGill University, Quebec, Canada. nancy.braverman@mcgill.ca
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Braverman
authors.forename: Maria Daniela
authors.initials: MD
authors.lastname: D'Agostino
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Maclean
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000818:Animals; D006801:Humans; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000187:drug effects / Q000235:genetics*; D018901:Peroxisomal Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015211:Zellweger Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism
chemical_list: D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human